No longer only known as drugs of abuse, psychedelic drugs increasingly are the subject of serious research as potential therapeutic agents. Monday’s symposium “Psychedelics in Medicine: Macroeconomics, Microdoses, and the Laboratory Perception” highlighted clinical, business, and laboratory implications of this emerging trend.
Psychedelic agents act by shifting neurochemical balance in the brain, inducing hallucinations and other sensory alterations. In addition to hallucinogens and dissociatives, current psychedelics researchers are studying also involve compounds that produce specific emotional reactions. These are called entactogens or empathogens and include drugs such as methylenedioxymethamphetamine (MDMA). Clinical trials focus on the short- and long-term effects of these drugs, particularly in patients with psychiatric disorders.
Speaker Dr. Steven Cotten opened the symposium with an overview of the business and regulatory aspects of this novel sector of drug development. He emphasized that drug patents should be of particular interest to laboratorians: As with the explosion of synthetic cannabinoids a decade ago, patented psychedelic derivatives could translate into novel sources of illicit drugs in the underground economy. “It could become a new cat and mouse game between the evolution of drug derivatives and the evolution of laboratory testing,” Cotten said.
The first psychedelic to enter clinical practice in the U.S. was SPRAVATO (esketamine), the S-enantiomer of ketamine, which is FDA-approved for use in treatment-resistant depression. As a dissociative hallucinogen, esketamine approval came with a Boxed Warning about the risk of sedation and difficulties with attention, judgement, and thinking. Cotten noted that the controversial approval of esketamine paved the way for other candidates in the drug development pipeline, such as MDMA, N,N-dimethyltryptamine (DMT), psilocybin, and derivatives.
While supervised administration and microdosing of these compounds might avoid the need for traditional therapeutic drug monitoring, laboratories performing testing could face novel challenges due to structural similarities and the need for enantiomeric separation.
In addition, recent patents for deuterated forms of DMT, psilocybin, and other psychedelics could introduce a novel complication for clinical laboratories. Heavy-isotope pharmaceuticals are intended in part to ensure labs can differentiate between prescribed and illicit sources of controlled substances. Given that most clinical assays only target labeled compounds as internal standards, approval of these drugs could require extensive validation and expansion of current testing.
Another speaker, Dr. Frederick Strathmann, tackled clinical and forensic laboratory considerations for psychedelic therapeutics. Strathmann started with an anecdote that re-framed his perception of how labs should approach compounds previously limited to recreational settings. After offering a researcher standard drug screens to detect MDMA, he received an upset response: “This is not drug abuse testing, this is a clinical trial.”
In his talk, Strathmann outlined how this shift in mindset includes a need for assays, test names, and interpretive reports geared for therapeutic applications of these drugs.
The final speaker, Dr. Kim Kuypers, described current clinical research into full and micro doses of psychedelics as potential therapeutic agents for psychiatric and neurological disorders. She noted psychedelics show promise in overcoming challenges of conventional treatments for mental health conditions. Medications such as antidepressants have slow onset of therapeutic benefit and require lengthy treatment. In contrast, studies of psychedelics have shown evidence of both rapid and persistent responses after only 1-2 doses. “I think this will be the future of psychiatry,” Kuypers said, but she also emphasized the studies still needed to validate these drugs for clinical use.
The entry of psychedelic drugs into the realm of prescribed therapeutics could have significant implications for clinical laboratories. As this session outlined, paying attention to emerging agents and ongoing clinical trials now could save labs a bad trip in years to come.